A Research Paper Published in International Journal of Biological Macromolecules

The focus of this study is on protein-DNA interactions that enable the transcription factor MntR from the bacterium Halalkalibacterium halodurans to function as a manganese metallosensor, which regulates manganese ion homeostasis in the bacterium. The research was based on computational methods, mostly molecular dynamics simulations, protein-DNA docking calculations, and quantum mechanical calculations aimed at obtaining parameters for describing interactions between amino acids and manganese ions. Simulations were conducted on various forms of the protein depending on the presence or absence of manganese ions in interaction with DNA. In addition to classical molecular dynamics simulations of protein-DNA complexes, simulations of protein-DNA complex formation were also carried out. The results provided insight into the molecular basis of the interaction between the H. halodurans MntR protein and DNA, and allowed the postulation of a model explaining the differences in protein-DNA interactions depending on the presence or absence of manganese ions in the protein’s binding sites. The simulation results show that even in the absence of manganese ions, the MntR protein interacts with DNA, but these interactions are non-specific and unstable. On the other hand, the presence of manganese ions induces changes in the dynamic and structural properties of the H. halodurans MntR protein, leading to the formation of stable and specific interactions with DNA, ultimately enabling the protein to fulfill its role as a transcription factor.

The published results were obtained as part of research conducted within the framework of the project "Manganese Metallosensors" (IP-2020-02-3446) funded by the Croatian Science Foundation, and represent the core of the doctoral thesis of Martina Manenica conducted under the supervision of Branimir Bertoša.